Technical Field
The present disclosure relates to devices and methods for palpation of tissues for characterization (e.g., qualification and/or quantification) of subcutaneous structures and, in particular, to a device and method including a tonometric lens configured to impinge upon tissues of interest for visualization and/or characterization of subcutaneous structures therein.
Background
Based on current incidence rates, 12.4% (e.g., one out of every eight women born in the United States today) will develop breast cancer at some time during her life. N. Howlader, A. Noone, and M. Krapcho, “SEER Cancer Statistics Review, 1975-2009,” Bethesda, Md., 2012. Despite advances in imaging technologies and clinical practice, breast cancer screening has shown a minimal and inconsistent impact in decreasing breast cancer-associated deaths while accumulating nearly $8 billion in associated annual costs. Specifically, the American Cancer Society estimates that 232,340 women were affected in 2013 by first diagnoses of breast cancer. For each woman, the estimated cost of treatment ranges from $20,000 to $100,000 with annual economic burden of breast cancer in the United States upwards of $20 billion. J. D. Campbell and S. D. Ramsey, “The costs of treating breast cancer in the US: a synthesis of published evidence,” Pharmacoeconomics, vol. 27, no. 3, pp. 199-209, January 2009. The earlier the breast cancer is detected, the better the clinical outcome and the lower the cost. L. Ries, J. J. Young, G. Keel, M. Eisner, Y. Lin, and M.-J. Horner, “Cancer Survival Among Adults: US SEER Program, 1988-2001,” Patient Tumor Charact. Natl. Cancer Institute, SEER Program, NIH, no. 07, 2007. In an effort to diagnose early stages of the disease, more than $7.8 billion of the spending was attributable to screening practices in 2010. C. O'Donoghue and M. Eklund, “Aggregate cost of mammography screening in the United States: comparison of current practice and advocated guidelines,” Ann. Intern. Med., pp. 145-154, 2014. Although screening has increased the incidence of early-stage cancers detected, one study showed only 8 of 122 early stage cancers diagnosed would have progressed to an advanced stage of the disease, a mere 7%. The same study estimates that as many as one third of all patients treated for breast cancer may be over-diagnosed. A. Bleyer and H. G. Welch, “Effect of three decades of screening mammography on breast-cancer incidence,” N. Engl. J. Med., vol. 367, no. 21, pp. 1998-2005, November 2012.
The two most common methods of population-wide screening are mammographic imaging and breast self-examination (BSE). As tissues become more cancerous and diseased, cells become necrotic to become denser and stiffer. Measured sensitivity and specificity values vary significantly with breast density, skill and experience of the radiologist and the quality of equipment used. W. E. Barlow, C. Chi, P. a Carney, S. H. Taplin, C. D'Orsi, G. Cutter, R. E. Hendrick, and J. G. Elmore, “Accuracy of screening mammography interpretation by characteristics of radiologists,” J. Natl. Cancer Inst., vol. 96, no. 24, pp. 1840-50, December 2004. Risks of screening include those associated with radiation exposure, psychological stress from false positive findings, and any harms from unnecessary treatment. See, e.g., P. Gøtzsche and M. Nielsen, “Screening for breast cancer with mammography,” Cochrane Database Syst Rev, no. 6, 2009, and L. Pace and N. Keating, “A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions,” JAMA, vol. 311, no. 13, pp. 1327-1335, 2014. There is even indication that women genetically predisposed to breast cancer with the BRCA1/2 mutation are twice as likely to develop cancer in response to radiographic screening if exposed before the age of 30. A. Pijpe, N. Andrieu, D. F. Easton, A. Kesminiene, E. Cardis, S. Peock, P. Manders, I. Thierry-chef, M. Hauptmann, D. Goldgar, M. A. Rookus, and F. E. Van Leeuwen, “Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK),” vol. 345, no. October, p. 2012, 2012. BSE intuitively utilizes the increased stiffness of the lesion by using tactile feedback to feel for “lumps.” Although BSE is advocated as an affordable method of screening, it is also associated higher biopsy rates, an increased chance of referral to mammography, and patient stress. V. Rosolowich, R. Lea, P. Levesque, F. Weisberg, J. Graham, and L. McLeod, “SOGC COMMITTEE OPINION: Breast Self-Examination,” J Obs. Gynaecol, vol. 28, no. 181, pp. 728-730, 2006. Further, because women are generally reluctant to self-refer for mammography, the primary care physician (PCP) is the primary gateway to screening. S. Nass, I. Henderson, and J. Lashof, Mammography and beyond: developing technologies for the early detection of breast cancer. 2001, p. 312. However, the PCP must rely on physical examination to make the determination that a patient may be developing a cancerous lesion. Without any quantitative evidence, he/she must convince the patient based on his/her qualitative assessment of a palpable mass. No method is currently used to aid clinical inspections to quantify the shape and mechanical characteristics of the interrogated tissue, rendering it an inherently qualitative test.
Although many professionals continue to advocate for one or both screening practices, clinical trials evaluating mammography and BSE have found increased incidence of early-stage cancers detected, yet results vary from a 19% reduction in mortality to no significant effect on survival rates. See, A. Pijpe, N. Andrieu, D. F. Easton, A. Kesminiene, E. Cardis, S. Peock, P. Manders, I. Thierry-chef, M. Hauptmann, D. Goldgar, M. A. Rookus, and F. E. Van Leeuwen, “Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK),” vol. 345, no. October, p. 2012, 2012; a.B. Miller, C. Wall, C. J. Baines, P. Sun, T. To, and S. a. Narod, “Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial,” Bmj, vol. 348, no. February 11 9, pp. g366-g366, February 2014; and S. VF, M. AG, M. VM, P. SA, K. RS, S. IK, P. RT, M. NSh, O. AA, B. NIu, I. OA, and I. VG, “Results of a prospective randomized investigation [Russia (St. Petersburg)/WHO] to evaluate the significance of self-examination for the early detection of breast cancer,” Vopr Onkol., vol. 49, no. 4, pp. 434-41, 2003. Even despite mammographic screening practices, 43% of identified cancers continue to present as symptomatic, including palpable masses. K. L. Mathis, T. L. Hoskin, J. C. Boughey, B. S. Crownhart, K. R. Brandt, C. M. Vachon, C. S. Grant, and A. C. Degnim, “Palpable presentation of breast cancer persists in the era of screening mammography,” J. Am. Coll. Surg., vol. 210, no. 3, pp. 314-8, March 2010. In light of the mixed results for population-wide screening, the question remains: how to improve clinical outcomes from screening while preventing needless tests or treatment and minimizing the associated harms? A growing consensus acknowledges the importance of BSE and mammography, but calls for alternative and complimentary decision-making tools to help guide patients and their physicians. See, J. D. Campbell and S. D. Ramsey, “The costs of treating breast cancer in the US: a synthesis of published evidence,” Pharmacoeconomics, vol. 27, no. 3, pp. 199-209, January 2009; A. Pijpe, N. Andrieu, D. F. Easton, A. Kesminiene, E. Cardis, S. Peock, P. Manders, I. Thierry-chef, M. Hauptmann, D. Goldgar, M. A. Rookus, and F. E. Van Leeuwen, “Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK),” vol. 345, no. October, p. 2012, 2012; and D. Kardinah, B. O. Anderson, C. Duggan, I. Ali, and D. B. Thomas, “Short report: Limited effectiveness of screening mammography in addition to clinical breast examination by trained nurse midwives in rural Jakarta, Indonesia,” Int. J. Cancer, vol. 134, no. 5, pp. 1250-5, March 2014. Information about the lesion, such as size, is an important factor in stratifying risk, and mortality that is not considered in current screening practices. L. Ries, J. J. Young, G. Keel, M. Eisner, Y. Lin, and M.-J. Horner, “Cancer Survival Among Adults: US SEER Program, 1988-2001,” Patient Tumor Charact. Natl. Cancer Institute, SEER Program, NIH, no. 07, 2007. By quantifying palpable masses and their changes over time, we intend to stratify risk and bridge the technology gap between BSE and mammography for palpable lesions.
Other imaging methods for screening exist, such as MRI and ultrasound, but are prohibitively expensive for population-wide screening and work best in conjunction with other screening methods. Experimental impedance measurement and thermography methods have been attempted but have never gained acceptance for use in a clinical setting due to low specificity. Tactile sensing methods to detect stiffer tissues based on mechanical properties have been developed and evaluated. For example, there is an FDA-cleared elastography technology system that uses a force sensor array in a hand-held system to characterize stiffer tissues. The commercial name of the system is SureTouch. See, M. Ayyildiz, B. Guclu, M. Z. Yildiz, and C. Basdogan, “A Novel Tactile Sensor for Detecting Lumps in Breast,” pp. 367-372, 2010; V. Egorov, T. Kearney, S. B. Pollak, C. Rohatgi, N. Sarvazyan, S. Airapetian, S. Browning, and A. Sarvazyan, “Differentiation of benign and malignant breast lesions by mechanical imaging,” Breast Cancer Res. Treat., vol. 118, no. 1, pp. 67-80, November 2009; and A. Sarvazyan, V. Egorov, and N. Sarvazyan, “Tactile Sensing and Tactile Imaging in Detection of Cancer,” in Biosensors and Molecular Technologies for Cancer Diagnostics, 2011, pp. 339-354. Another device, the Intelligent Breast Exam (iBE) system, uses a piezoelectric force sensor array to detect changes in mechanical properties of tissues. X. Xu, C. Gifford-Hollingsworth, R. Sensenig, W.-H. Shih, W. Y. Shih, and A. D. Brooks, “Breast tumor detection using piezoelectric fingers: first clinical report,” J. Am. Coll. Surg., vol. 216, no. 6, pp. 1168-73, June 2013. Both devices share a similar method and subsequent flaw: the resolution of the device is limited by the number or density of force sensors in the array. Tracking changes in shape or size with these devices would be either expensive to fabricate a probe with high sensor density, or insensitive. Furthermore, neither device is intended for use by a patient. A device that is inexpensive, user-friendly, and that can be used in the home would allow more frequent measurements with fewer clinical visits.
While it is evident that experts disagree about the balance between advantages and drawbacks to each mammographic and BSE screening procedures, there is general agreement that complimentary methods of lesion assessment to improve clinical outcomes are desirable. An opportunity exists for non-invasive and inexpensive evaluation of palpable lesions through tactile sensing. Existing devices fail to provide the basis for a model that includes both home and clinical monitoring over time.